Derivatives of 2-oxocyclopentane carboxylic acid

ABSTRACT

LOWER ALKYL ESTERS OF 2-OXOCYCLOPENTENE CARBOXYLIC ACID CYANOACETHYDRAZONE, PREPARED FROM THE CORRESPONDING LOWER ALKYL ESTER OF 2-OXOCYCLOPENTATE CARBOXYLIC ACID AND CYANOACETHYDRAZIDE. THE COMPOUNDS ARE USEFUL AS ANTI-PARASITIC AGENTS.

United States Patent Ofice 3,580,945 Patented May 25, 1971 3,580,945 DERIVATIVES F Z-OXOCYCLOPENTANE CARBOXYLIC ACID Real Laliberte, Laval, Quebec, Canada, assignor to Ayerst, McKenna & Harrison, Ltd., St. Laurent, Quebec, Canada No Drawing. Filed Mar. 21, 1969, Ser. No. 809,412 Int. Cl. C07c 121/46 U.S. Cl. 260-464 3 'Claims ABSTRACT OF THE DISCLOSURE Lower alkyl esters of 2-oxocyclopentane carboxylic acid cyanoacethydrazone, prepared from the corresponding lower alkyl ester of 2-oxocyclopentane carboxylic acid and cyanoacethydrazide. The compounds are useful as anti-parasitic agents.

BACKGROUND OF THE INVENTION This invention relates to derivatives of 2-oxocyclopentane carboxylic acid, in particular to the cyanoacethydrazone of the lower alkyl esters of said acid. Those compounds are useful as anti-parasitic agents of exceptionally low toxicity, in particular as anthelminthic agents especially active against certain types of oxyuridae such as Syphacia obvelata.

SUMMARY OF THE INVENTION The compounds of this invention may be represented by the formula COOR in which R represents a lower alkyl group. They are conveniently prepared by reacting the corresponding lower alkyl ester of 2-oxocyclopentane carboxylic acid with cyanoacethydrazide.

DETAILED DESCRIPTION OF THE INVENTION More specifically, I prefer to react a 2-carbo(1ower alkoxy)cyclopentanone with approximately one equivalent of cyanoacethydrazide in solution in a lower alkanol, preferably ethanol, heating the mixture, preferably to reflux, for periods of time of from one to five hours, preferably three hours, and cooling; the resultant lower alkyl ester of 2oxocyclopentane carboxylic acid cyanoacethydrazone is then filtered and recrystallized from a lower alkanol, preferably isopropanol.

When testing the compounds of this invention in standard pharmacological tests, for example in the test for determining anti-parasitic activity, especially anthelminthic activity in mice described by J. S. Steward in Pharasitology, vol. 45, p. 231 (1955) they have exhibited utility as antiparasitic agents.

When the compounds of this invention are employed as anti-parasitic agents in warm-blooded animals, e.g. mice alone or in combination with pharmacologically acceptable carriers, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard biological practice. For example, they may be administered orally in solid form containing such excipients as starch, milk sugar, certain types of clay and so forth. They may also be administered orally in the form of solutions or they may be injected parenterally. For parenteral administration they may be used in the form of a sterile solution containing other solutes, for example, enough saline or glucose to make the solution isotonic.

The dosage of the present anti-parasitic agents will vary with the form of administration and the particular compound chosen. Furthermore, it will vary with the particular host under treatment. Generally, treatment is initiated with small dosages substantially less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. In general, the compounds of this invention are most desirably administered orally at a concentration level that will generally afford effective results Without causing any harmful or deleterious side effects and preferably at a level that is in a range of from about 50 mg. to about 500 mg. per kilo per day, although as aforementioned variations will occur. However, a dosage level that is in the range of from about mg. to about 300 mg. per kilo per day is most desirably employed in order to achieve effective results.

The following formulae, in which R has the significance defined above, and example will illustrate this invention:

000R COOR EXAMPLE 1 2-oxocyclopentane carboxylic acid methyl ester cyanoacethydrazone The methyl ester of 2-oxocyclopentane carboxylic acid (0.01 mole) is added to 0.01 mole of cyanoacethydrazide in 50 mls. of ethanol. The mixture is refluxed for three hours, and then cooled. The solid is filtered off and crystallized from isopropanol, to yield 2-oxocyclopentane carboxylic acid methyl ester cyanoacethydrazone, M.P. 111 C. Calculated (percent): C, 55.69; H, 6.26; N, 18.23. Found (percent): C, 55.68; H, 6.37; N, 17.71.

In the same manner, by using the ethyl, propyl, isopropyl, or butyl esters of 2-oxocyclopentane carboxylic acid as starting material the corresponding ethyl, propyl, isopropyl, and butyl esters of 2-oxocyclopentane carboxylic acid cyanoacethydrazone are also obtained.

I claim:

1. A compound selected from those of the formula COOR 3. The process of preparing a compound of the formula 4 wherein R represents a lower alkyl group, which com- References Cited prises bringing together, in solution in lower alkanol and at an elevated temperature, above room temperature, ap- UNITED STATES PATENTS proximately one molar equivalent of cyanoacethydrazide 3,489,814 1/1970 Pews et a1. 260-464X and a 2-carbo (lower alk0xy)cyclopentanone of formula 5 JOSEPH P. BRUST, Primary Examiner US. Cl. X.R.

wherein R represents lower alkyl. 10 

